The proposed project will continue development of the methodology for the determination of detailed molecular structures in non-crystalline environments. Principally, this entails two-dimensional nuclear magnetic resonance techniques analyzed in detail with a complete relaxation matrix analysis and used in conjunction with distance geometry, molecular mechanics and molecular dynamics calculations. Specifically, the methodology will be applied to the investigation of nucleic acid fragments, with an emphasis on those containing adenine (A) or thymine (T). Although related DNA fragments will constitute the majority of studies, analogous RNA and RNA-DNA hybrids will also be subjects for study. Further studies will include modified bases. Finally, binding of drugs which show preference to AT moieties of DNA will be investigated.